Antibodies targeting extractable nuclear antigens: historical development and current knowledge.
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Antibodies, Antinuclear↗
Biomedical subjects
R Bauer
Publications and source records attributed to R Bauer.
Growth optimization of Pediococcus damnosus NCFB 1832 and the influence of pH and nutrients on the production of pediocin PD-1.
AIMS: Optimization of the growth of Pediococcus damnosus NCFB 1832 and the production of pediocin PD-1 by traditional fermentation methods. METHODS AND RESULTS: Fermentation studies were conducted in De Man Rogosa and Sharpe (MRS) broth (Oxoid), preadjusted to specific pH values, and in MRS broth supplemented with various nitrogen sources, MnSO4, MgSO4 and Tween 80. The production of pediocin PD-1 closely followed the growth curve of Ped. damnosus NCFB 1832. Maximum levels of bacteriocin activity (3249 AU ml(-1)/O.D.max) were recorded in MRS broth with an initial pH of 6.7. In media with an initial pH of 4.5 bacteriocin activity as low as 222 AU ml(-1)/O.D.max was recorded. The highest bacteriocin activity was recorded in growth conditions allowing the greatest pH variation (highest DeltapH). The addition of bacteriological peptone (1.7%, w/v), MnSO4 (0.014%, w/v) and Tween 80 (3%, v/v) to MRS and adjustment of the medium pH to 6.7 resulted in a further increase in activity (from 3249 to 5078 AU ml(-1)/O.D.max). The same medium, but with an initial pH of 6.2, resulted in an 82.5% decrease in bacteriocin activity. CONCLUSIONS: Pediocin PD-1 production is not only stimulated by the presence of specific growth factors (e.g., bacteriological peptone, MnSO4 or Tween 80), but may also be stimulated by the lowering in pH during growth (highest DeltapH), and thus also the amount of organic acids produced. SIGNIFICANCE AND IMPACT OF THE STUDY: The production of pediocin PD-1 by the wild-type producer strain was significantly improved by using a defined medium and traditional fermentation methods.
Anti-Bacterial Agents↗
Inhibitory effects of maesanin and analogs on arachidonic acid metabolizing enzymes.
The substituted 1,4-benzoquinone, maesanin (1), is a potent 5-lipoxygenase (5-LO) inhibitor present in the fruit of Maesa lanceolata Forssk. Thirteen natural, synthetic, semisynthetic, and microbially transformed analogs of 1 were tested for their in vitro inhibition of 5-lipoxygenase (5-LO) and cyclooxygenase-1 (COX-1). Maesanin was the most active 5-LO inhibitor. All other analogs were inactive or less active than the natural products as 5-LO inhibitors. None of the tested compounds was strongly active in the COX-1 inhibition assay.
Animals↗
Further phenols and polyacetylenes from the rhizomes of Atractylodes lancea and their anti-inflammatory activity.
From the rhizomes of Atractylodes lancea, 2-[(2'E)-3',7'-dimethyl-2',6'-octadienyl]-4-methoxy-6-methylphenol (1) was isolated as a new natural product. The compound showed strong inhibitory effects on 5-lipoxygenase (5-LOX) and cyclooxygenase-1 (COX-1), but exhibited only weak antioxidative activities [IC50 = 0.1 microM (5-LOX), 2 microM (COX-1), 9 microM (PMN/FMLP), 28 microM (PMNIOZ)]. Moreover, five new acetylenes were isolated and elucidated as (3Z,5E,11E)-tridecatriene-7,9-diynyl-1-O-(E)-ferulate (2), erythro-(1,3Z,11E)-tridecatriene-7,9-diyne-5,6-diyl diacetate (3), (1Z)-atractylodin (4), (1Z)-atractylodinol (5), (1Z)-acetylatractylodinol (6) plus the known (4E,6E,12E)-tetradecatriene-8,10-diyne-1,3-diyl diacetate (7). Among the acetylenes, only 2 showed strong inhibition of 5-LOX and COX-1 activity (IC50 (5-LOX) = 3 microM, IC50 (COX-1) = 1 microM). In addition, the fatty acids linoleic acid, oleic acid and palmitic acid with previously established 5-LOX-/COX-1 inhibitory actions were identified as major constituents of the n-hexane extract and thus seem to contribute to the plant's in vitro activity.
Acetylene↗
A reappraisal of neonatal blood chemistry reference ranges using the Nova M electrodes.
The objective of this study is to establish new reference ranges for whole blood electrolytes, gases, and selected chemistries in normal healthy newborn infants obtained from cord blood and at 2-4 hours of life based on modern analytic techniques. Healthy appropriate-for-gestational age (AGA), term infants were studied. Whole venous cord blood and blood drawn at 2-4 hours of life were analyzed for gases, sodium, potassium, chloride, ionized calcium, ionized magnesium, hemoglobin, and hematocrit. Concentrations for blood glucose and blood urea nitrogen were close to older published concentrations. Na(+), K(+), and Cl(-) were significantly different and had much narrower normal margins. New norms are included for blood gases, lactate, iCa, and iMg. We offer a range of values for often-measured blood chemistries in term, healthy infants, using modern laboratory methods. These values could serve as more up-to-date references compared with older values found in major textbooks of Neonatology.
Blood Chemical Analysis↗
Absorption of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides after oral application of Echinacea purpurea tincture.
Alkamides are suspected to contribute to the activity of Echinacea preparations. In preliminary experiments a quantification method for dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides in human blood has been developed by which it was possible to detect dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides in human blood after oral application of Echinacea purpurea mother tincture.
Administration, Oral↗
The treatment of moderate to severe psoriasis with a new anti-CD11a monoclonal antibody.
BACKGROUND: Anti-CD11a (hu1124) is a humanized monoclonal antibody directed against the CD11a subunit of LFA-1. This study investigated whether treatment with anti-CD11a antibody provides clinical benefit to patients with moderate to severe plaque psoriasis. METHODS: This was a double-blind, placebo-controlled, phase II, multicenter study. In total, 145 patients with minimum Psoriasis Area and Severity Index scores of 12 and affected body surface area of 10% or more were sequentially enrolled into low-dose (0.1 mg/kg, n = 22) or high-dose (0.3 mg/kg, n = 75) groups. Within groups, patients were randomized to treatment or placebo (n = 48) in a 2:1 ratio. Drug was administered intravenously at weekly intervals for 8 weeks. RESULTS: The percentage of subjects achieving more than 50% improvement in physician's global assessment at day 56 (1 week after final dose) was 15% and 48% for placebo and 0.3 mg/kg of drug, respectively (P =.002). A physician's global assessment of excellent (>75% improvement) was greater in the 0.3 mg/kg group versus placebo (25% vs 2%, P =.0003). Average Psoriasis Area and Severity Index scores at day 56 were 13.9 +/- 7.5 (placebo) and 10.9 +/- 8.4 (0.3 mg/kg) (P <.0001). Epidermal thickness was reduced in the 0.3 mg/kg group compared with the placebo group (37% vs 19%, P =.004). Treatment was well tolerated; mild to moderate flu-like complaints were the most common adverse events. White blood cell counts and lymphocyte counts transiently increased. Depletion of circulating lymphocytes did not occur. CONCLUSIONS: Anti-CD11a antibody administered intravenously in 8 weekly doses of 0.3 mg/kg was well tolerated and induced clinical and histologic improvements in psoriasis.
Adult↗
Oxidative state and histological changes in muscles of mastication after conditioning training.
Stress due to endurance training of striated muscles leads to adaptive changes in the distribution of muscle fiber types (i.e. ratio of type I and type II fibers). Moreover, severe training leads to tissue hypoxia and oxidative stress in muscles. In the current study, we examined the relationship between histological changes and oxidative state in muscles of mastication during the acute adaptation phase to a sustained muscle load. Six domestic pigs received build-ups on the molar teeth in order to induce a sustained load of the muscles of mastication for a duration of four weeks. Afterwards the masseter (M1, M2, M3), medial pterygoid (PM), temporal (TP1, TP2), and geniohyoid muscles (GH) were removed and the fiber type distribution was determined by enzyme histochemistry. Additionally, the tissue content of glutathione and lipid peroxidation (LPO) products were measured. The above treatment led to muscle fiber transformation of type II into type I (M1, M2, TP2, PM) and a decrease of the GSH content (M1, M2 and TP2). The changes in the GSH/GSSG ratio were in accordance with the changes in proportions of muscle fiber types, with the lowest GSH/GSSG ratios in the most stressed muscles of the treated animals. No significant changes in LPO products were found. The decrease of the GSH/GSSG ratio in the most stressed muscles indicates an increased intracellular oxidative stress, which may be caused by tissue hypoxia during the chronic phase of muscle adaptation.
Adaptation, Physiological↗
Effects of 28-day mechanical and chewing stress on content of bound and diffusible ions in muscles of mastication.
Type I and type II muscle fibres have different ion concentrations. Muscles adapt to chronic stress by changing of fibre types and remodelling of the myosin heavy chains in the muscle fibres. The present investigation on ionic change during muscular contraction was carried out on 10-week-old pigs (6 treated animals, 6 controls) over a 28-day period. Six pigs received acrylic build-ups to induce mechanical advancement of the lower jaw and chronic chewing stress. Muscle tissue was taken from the masseter (M1, M2, M3), temporal (TP1, TP2), medial pterygoid (PM) and geniohyoid (GH) muscles by a standardized method. Eighty-four muscle samples were used for histological fibre differentiation with mATPase. Energy-dispersive X-ray microanalysis of muscles was carried out in an environmental scanning electron microscope. Endurance stress in the stressed muscles was seen as an increase of type I fibres (P < 0.001). This histological change and ionic alterations were measured in the anterior region of the masseter (M1 and M2) and in the posterior region of the temporal muscle (TP2). Smaller changes were found in the medial pterygoid muscle. We measured in this muscles increases in potassium, sulphur, chloride (P < 0.05) and even larger increases in phosphate (up to 1.5 mmol/g to 2.3 mmol/g, P < 0.001) and sodium (3-fold, P < 0.001). The results reveal the effects of chronic stress on muscle fibres and ion concentration in the muscle. Chronic stress resulted in an increase of type I fibres and increased ion concentration in the same muscle region. These are considered to be indicators of more efficient contraction. The changes in ion concentration are an important factor in muscle contraction.
Animals↗
The effects of increasing concentrations of isoflurane and desflurane on pulmonary perfusion and systemic oxygenation during one-lung ventilation in pigs.
UNLABELLED: During one-lung ventilation (OLV), hypoxic pulmonary vasoconstriction (HPV) reduces venous admixture and attenuates the decrease in arterial oxygen tension by diverting blood from the nonventilated lung to the ventilated lung. In vitro, desflurane and isoflurane depress HPV in a dose-dependent manner. Accordingly, we studied the effects of increasing concentrations of desflurane and isoflurane on pulmonary perfusion, shunt fraction, and PaO(2) during OLV in vivo. Fourteen pigs (30-42 kg) were anesthetized, tracheally intubated, and mechanically ventilated. After placement of femoral arterial and thermodilution pulmonary artery catheters, a left-sided double-lumen tube (DLT) was placed via tracheotomy. After DLT placement, FIO(2) was adjusted at 0.8 and anesthesia was continued in random order with 3 concentrations (0.5, 1.0, and 1.5 minimal alveolar concentrations) of either desflurane or isoflurane. Differential lung perfusion was measured with colored microspheres. All measurements were made after stabilization at each concentration. Whereas mixed venous PO(2), mean arterial pressure, cardiac output, nonventilated lung perfusion, and shunt fraction decreased in a dose-dependent manner, PaO(2) remained unchanged with increasing concentrations of desflurane and isoflurane during OLV. In conclusion, increasing concentration of desflurane and isoflurane did not impair oxygenation during OLV in pigs. IMPLICATIONS: In an animal model of one-lung ventilation, increasing concentrations of desflurane and isoflurane dose-dependently decreased shunt fraction and perfusion of the nonventilated lung and did not impair oxygenation. The decreases in shunt fraction are likely the result of anesthetic-induced marked decreases in cardiac output and mixed venous saturation.
Anesthetics, Inhalation↗
Taxonomic studies on the genus Cystofilobasidium: description of Cystofilobasidium ferigula sp. nov. and clarification of the status of Cystofilobasidium lari-marini.
A new species of the genus Cystofilobasidium is described as Cystofilobasidium ferigula sp. nov. The new taxon represents the teleomorphic stage of Cryptococcus ferigula and was obtained in mating experiments using three strains deposited in the Portuguese Yeast Culture Collection (mating types A1) and a recent isolate (mating type A2). Cystofilobasidium ferigula is characterized using an integrated approach encompassing morphological studies, investigation of the ultrastructure of the septal pore, a comparative study of physiological traits, determination of the DNA base composition, DNA reassociation experiments and PCR fingerprinting. During the course of this study, a close similarity of microsatellite-primed PCR fingerprints was detected between Cystofilobasidium lari-marini and Cystofilobasidium capitatum. DNA-DNA reassociation experiments gave high homology values, which indicates that Cystofilobasidium lari-marini must be regarded as a synonym of Cystofilobasidium capitatum.
Animals↗
Campylobacter upsaliensis exerts a cytolethal distending toxin effect on HeLa cells and T lymphocytes.
Campylobacter upsaliensis is an emerging human enteropathogen. However, little is known about the pathogenesis of C. upsaliensis infection. In this study the authors demonstrate that C. upsaliensis whole-cell preparations and extracts produce a cytolethal distending toxin (CDT)-like effect on HeLa cells characterized by progressive distension and nuclear fragmentation culminating in cell death over 5 d. To further delineate the nature of this toxic effect in relation to CDT from other pathogens, the effect of C. upsaliensis on cellular events in epithelial cells and immunocytes was investigated. C. upsaliensis lysate-treated HeLa cells subjected to FACScan analysis using carboxyfluorescein diacetete succinimidyl ester (CFDA-SE) as a cell tracer demonstrated cell division arrest. Propidium iodide (PI) staining of HeLa cells revealed that cell cycle arrest occurred in G(2)/M. Human T lymphocytes exposed to C. upsaliensis lysates also showed cell cycle arrest in G(2)/M. Using a combination of Annexin V/PI staining and TUNEL assay, cytodistended HeLa cells were shown to undergo apoptotic cell death. These data provide the first insights into the virulence mechanisms of this novel enteropathogen.
Bacterial Toxins↗
Conformational characterization of oligomeric intermediates and aggregates in beta-lactoglobulin heat aggregation.
In one of the first studies of isolated intermediates in protein aggregation, we have used circular dichroism and fluorescence spectroscopy to characterize metastable oligomers that are formed in the early steps of beta-lactoglobulin heat aggregation. The intermediates show typical molten globule characteristics (secondary structure content similar to the native and less tight packing of the side chains), in agreement with the belief that partly folded states play a key role in protein aggregation. The far-UV CD signal bears strong resemblance to that of a known folding intermediate. Cryo-transmission electron microscopy of the aggregates reveals spherical particles with a diameter of about 50 nm and an internal threadlike structure. Isolated oligomers as well as larger aggregates bind the dye thioflavin T, usually a signature of the amyloid superstructures found in many protein aggregates. This result suggests that the structural motif recognized by thioflavin T can be formed in small oligomers.
Animals↗
Effects of impulse noise stimulation on electrocorticogram and heart rate.
It is now recognized that high-level impulse noises penetrate the uterus of pregnant sheep, elevate thresholds of fetal auditory-evoked potential and produce damage to fetal inner ear hair cells. However, little is known about functional effects of airborne impulse noise on the late-term fetus. In the present study, the effects of a series of 20 impulses on the behavioral state of 6 fetal sheep were tested. Noise impulses produced 169.3 peak sound pressure level (pSPL) in air. Peak levels recorded near the fetal head averaged 161.1 dB. Impulses delivered to the fetus during periods of NREM sleep resulted in a decrease in average fetal heart rate (FHR) from 185 +/- 22 beats/min (bpm) before stimulation to 174 +/- 23 bpm 2-5 s after stimulation (p < 0.05). During REM sleep, an FHR acceleration occurred (before stimulation: 177 +/- 24 bpm, after stimulation: 189 +/- 31 bpm; p < 0.05). Impulse exposure during NREM sleep resulted in reductions in delta-, theta- and alpha-band powers. As a consequence, total power decreased from 100 to 72 +/- 16% (p < 0.05). During REM sleep, stimulation provoked a short decrease in total band power from 100 to 73 +/- 20% and a similar decrease in the theta- and beta-band powers. The results indicated that impulse noise evoked short-term alterations in FHR and cortical activity. These changes were mediated by auditory brain stem activation that led to cortical desynchronization during both NREM and REM sleep in late-term fetal sheep.
Acoustic Stimulation↗
Prognostic value of soluble tumor necrosis factor receptors 1 and 2 in multiple sclerosis patients treated with interferon beta-1b.
The objective of this study was to investigate the effect of interferon (IFN) beta-1b on the serum levels of soluble tumor necrosis factor receptor 1 (sTNF-R1) and sTNF-R2 in patients with multiple sclerosis (MS) in correlation with clinical and magnetic resonance image (MRI) activity. Serum samples were obtained every 3 months from 24 patients treated with 8 x 10(6) U of IFN beta-1b every other day (treatment group) and from 21 patients without any immunomodulatory therapy (control group) over a 15-month observation period. The cytokine receptor levels were assessed by ELISA. Cranial MRI was performed every 6 months to determine the burden of disease. In the treatment group, the MRI responders had significantly larger mean values for the area under the concentration-time curve of sTNF-R1 (p = 0.04) and sTNF-R2 (p = 0.01) when compared to the MRI nonresponders during the 15-month observation period. With regard to an increase in sTNF-R1 and -2 of more than 20% during the first 3 months of treatment, we observed a sensitivity of 33 and 58%, respectively, a specificity of 90 and 60%, respectively, and a positive predictive value of 80 and 64%, respectively, for MRI response during the 15-month observation period. A decrease in sTNF-R1 and -2 of more than 20% during the first 3 months of treatment had a sensitivity of 40 and 20%, respectively, a specificity of 100 and 100%, respectively, and a positive predictive value of 100 and 100%, respectively, for further MRI nonresponse (during the 15-month observation period). The present data suggest that assessment of sTNF-Rs may contribute to the identification of subgroups of patients who are likely to respond better than others to treatment with IFN beta-1b. This could help to establish a cost-effective prescription pattern for this expensive treatment, which is of importance for the future management of patients with MS.
Adult↗
Intrauterine growth restriction induces up-regulation of cerebral aromatic amino acid decarboxylase activity in newborn piglets: [18F]fluorodopa positron emission tomographis study.
There is evidence that intrauterine growth restriction (IUGR) is associated with altered dopaminergic function in the immature brain. However, the relevant enzyme activities have not been measured in the living neonatal brain together with brain oxidative metabolism. Therefore, fluorine-18-labeled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) was used together with positron emission tomography to estimate the activity of the aromatic amino acid decarboxylase in the brain of 10 newborn IUGR piglets (2 to 5 d old; body weight, 908 +/- 109 g) and in 10 normal-weight (3 to 5 d old; body weight, 2142 +/- 373 g) newborn piglets. The regional transport of FDOPA to the brain and the clearance rate of labeled metabolites from brain tissue were broadly similar in the two groups. However, the regional rate constant for back flux from the brain was markedly increased in IUGR piglets for striatum (72%) and frontal cortex (83%) (p < 0.05). Furthermore, the rate constant for conversion of FDOPA to fluorodopamine was markedly increased (between 48% in cerebellum and 91% in mesencephalon, p < 0.05) in all brain regions of IUGR piglets studied. Thus, it is suggested that IUGR induces an up-regulation of aromatic amino acid decarboxylase activity that is not related to alterations in brain oxidative metabolism.
Animals↗
Gastrointestinal development in the Drosophila embryo requires the activity of innexin gap junction channel proteins.
Cell to cell communication plays an essential role during pattern formation and morphogenesis of the diverse tissues and organs of the body. In invertebrates, such as the fruitfly Drosophila, the direct communication of closely apposed cells is mediated by gap junctions which are composed of oligomers of the innexin family of transmembrane channel proteins. Few data exist about the developmental role of the eight innexin genes which have been found in the Drosophila genome. We have investigated the role of the innexin 2 and ogre genes during gastrointestinal development of the fly embryo. Our findings suggest that innexins are involved in the formation of the proventriculus, an organ that develops at the foregut/midgut boundary by migration of primordial cells and subsequent infolding of epithelial tissue layers.
Animals↗
[Antigranulocyte scintigraphy of septic loosening of hip endoprosthesis: effect of different methods of analysis].
AIM: Diagnosis of infection with help of antigranulocyte scintigraphy near body stem is difficult because of contemporary visualisation of bone marrow. Therefore, we investigated, whether it is possible to improve the accuracy in diagnosing septic loosening of hip endoprosthesis by changing the analyzing methods. METHODS: In 28 patients, the results of a visual interpretation of late scan, a visual interpretation and a quantitative interpretation of time-activity-course were compared. These results were verified by histology respectively microbiology. RESULTS: Histological and microbiological verification found 14 septic loosening and 14 aseptic loosening of the hip prothesis. Therefore, sensitivity, specificity, negative and positive predictive value for the visual interpretation of late scan were 0.86, 0.57, 0.80 and 0.67. For visual and quantitative interpretation of time-activity-course we found 0.86, 0.79, 0.85 and 0.80 respectively 1, 0.93, 1, 0.93. For interobserver agreement we found kappa coefficients of 0.28 +/- 0.2 for visual interpretation of late scan, 0.48 +/- 0.17 for visual interpretation and 1.0 +/- 0 for quantitative interpretation of time-activity-course. CONCLUSION: In all investigated values quantitative interpretation of time-activity-course was superior to the other analyzing methods. Therefore, antigranulocyte scintigraphy for septic loosening of hip endoprosthesis should be interpreted quantitatively.
Antibodies, Monoclonal↗